FDA approves amivantamab and hyaluronidase-lpuj for subcutaneous injection
Regulatory approval: On Dec 17, 2025, the FDA approved amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for subcutaneous injection for adult patients across all indications already approved for IV amivantamab (Rybrevant). The PALOMA-3 trial in EGFR-mutated locally advanced/metastatic NSCLC supported comparability of exposure and showed no notable differences in descriptive ORR/PFS analyses and no evidence of a detrimental OS effect versus IV dosing. Systemic administration reactions were lower with SC dosing.
FDA approval (Dec 17, 2025)
The FDA approved amivantamab and hyaluronidase-lpuj (Rybrevant Faspro, Janssen Biotech, Inc.) for subcutaneous injection for adult patients across all indications approved for the intravenous (IV) formulation of amivantamab (Rybrevant). Clinicians are directed to the prescribing information for the specific indications; full prescribing information will be posted on Drugs@FDA.
Supporting evidence: PALOMA-3
The subcutaneous formulation was evaluated in PALOMA-3, a randomized, open-label, multicenter, multiregional trial in adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. 418 patients were randomized 1:1 to SC amivantamab+hyaluronidase-lpuj plus lazertinib vs IV amivantamab plus lazertinib.
Primary outcome measures included pharmacokinetics (trough concentrations at steady state). At the recommended dosing schedules, geometric mean ratios (GMRs) for exposure metrics met the prespecified comparability threshold (lower bound >0.8), including AUCDay1–Day15 (Cycle 2) GMR 1.03 (90% CI 0.98–1.09) and steady-state Ctrough (Cycle 4 Day 1) GMR 1.43 (1.27–1.61) for q2w dosing.
Descriptive analyses reported no notable differences in ORR and PFS and no evidence of a potential detrimental effect on OS with SC vs IV.
Safety
Overall safety was generally similar between arms; systemic administration reactions occurred in 13% (SC) vs 66% infusion-related reactions (IV). Label warnings/precautions include hypersensitivity/administration-related reactions, ILD/pneumonitis, VTE with concomitant lazertinib, dermatologic reactions, ocular toxicity, and embryo-fetal toxicity.
Review pathway
The review was conducted under Project Orbis, with collaboration noted with Australia’s TGA and Health Canada (reviews may be ongoing).